The distribution of the activity of brain hexokinase between soluble and mitochondrial forms is at least partially governed by metabolic activity, increased amounts of the particulate enzyme being observed during times of increased glycolytic activity. These changes may be involved in regulation of activity and are thought to result from alteration in intracellular levels of various metabolites (e.g., glucose-6-P, Pi) previously shown to influence this distribution in vitro. The importance of the primary structure and conformation of the enzyme, and the role of divaltn cations and various membrane constituents (e.g., lipids, proteins, glycoproteins) in this membrane-enzyme interaction will be investigated. The outer mitochondrial membrane has been shown to specifically interact with the hexokinase; microsomal or synaptosomal membranes, or the inner mitochondrial membranes exhibit greatly decreased binding capacity. Studies will be directed at ascertaining which components(s) (i.e., proteins, lipids, etc.) of the outer mitochondrial membrane is (are) responsible for the specificity of interaction. BIBLIOGRAPHIC REFERENCES: Wilson, J.E., Wilkin, G.P. and Balazs, R. (1976) Metabolic Properties of a Purified Preparation of Large Fragments of the Cerebellar Glomeruli: Glucose Metabolism and Amino Acid Uptake, J. Neurochem. 26, 957-965. Felgner, P.L. and Wilson, J.E. (1976) Purification of Nonbindable and membrane-Bindable Mitochondrial Hexokinase from Rat Brain, Biochem. Biophys. Res. Commun. 68, 592-597.